Wnt-driven intestinal tumourigenesis is suppressed by Chk1 deficiency but enhanced by conditional haploinsufficiency.
Oncogene
; 33(31): 4089-96, 2014 Jul 31.
Article
in En
| MEDLINE
| ID: mdl-24037525
ABSTRACT
Chk1 is essential in maintaining genomic stability due to its role in cell cycle regulation. Several recent studies have indicated that the abrogation of checkpoints in tumourigenesis through the inhibition of Chk1 may be of therapeutic value. To further investigate the role of Chk1 in the mouse small intestine and its potential role as a therapy for colorectal cancer, we simultaneously deleted Chk1 and Apc in the mouse small intestine. We found that homozygous loss of Chk1 is not compatible with Wnt-driven proliferation and resulted in the suppression of Wnt-driven tumourigenesis in the mouse small intestine. In contrast, heterozygous loss of Chk1 in a Wnt-driven background resulted in an increase in DNA damage and apoptosis and accelerated both tumour development and progression.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Kinases
/
Cell Transformation, Neoplastic
/
Adenomatous Polyposis Coli Protein
/
Wnt Proteins
/
Haploinsufficiency
/
Intestine, Small
Limits:
Animals
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2014
Document type:
Article
Affiliation country:
United kingdom